Feline leukemia virus (FeLV) was first isolated in 1964 from cats with lymphoid malignancies. It was subsequently shown that a proportion of cats inoculated with FeLV would develop lymphoid neoplasms after a latent period of many weeks or months. In 1970, a simple blood test was developed to detect cats that were infected with FeLV. After screening many cats, it became apparent that lymphoid tumors represented only a fraction of the disease caused by FeLV. Conditions related to FeLV infection included anemia, myeloproliferative disorders, and reproductive problems in queens. In addition, a marked proportion of cats suffering from a wide range of infective diseases were found to be concurrently infected with FeLV. The pathogenesis of FeLV infection in nature has been the topic of many reports. In the cat population, FeLV appears to be widespread, and horizontal transmission from cat to cat is apparently the major mode of infection. After exposure, cats develop immunity to the virus or become chronically infected. Many of the chronically infected cats eventually succumb from various disorders, but others remain asymptomatic for extended periods. Pedersen et al, Am. J. Vet. Research, 38, 1523-1531 (1977).
The morbidity and mortality from FeLV infection is related to the density of the cat population study. The virus is prevalent in urban areas, and in multiple cat households and catteries. In these environments almost all exposed cats will become infected, and 30% or more of them will become persisently viremic. Hardy et al, Nature, 244, 266-267 (1973). Therefore, a vaccine which was capable of preventing persistent feline leukemia viremia would be of great value.
Previous attempts to prepare vaccines for feline leukemia have been directed to preventing the FeLV infection, and/or the tumors which may develop if a persistent infection develops. The effectiveness of vaccines for feline leukemia have been evaluated in terms of the serum antibody titer to feline oncorna virus-associated cell membrane antigen (FOCMA), and virus neutralizing antibody titer (VN), or by challenge of inoculated cats with injections of virulent feline sarcoma virus (FeSV) or virulent FeLV. No study has been reported in which the effectiveness of feline leukemia vaccines for preventing persistent infection has been specifically evaluated, and there is no report of a challenge test by natural infection.
It has been reported that an effective vaccine against feline leukemia virus can use a cell membrane antigen system. Jarrett et al, Int. J. Cancer, 16, 134-141 (1975). The cell-type vaccines of Jarrett et al were prepared from a feline lymphoblastoid cell line permanently infected with FeLV (the FL74 cell line). FOCMA antibody titers were determined after administration of the FL74 cell vaccines for both live cells and cells treated with formaldehyde. Tests were also made with FeLV produced by the FL74 cells and separated from the cells for vaccine preparation. However, Jarrett et all concluded: "The high antigenicity of intact FL74 cells and, in contrast, the very low antigenicity of the virus purified from those cells, were shown in the present experiments. The purified virus failed to induce any demonstrable antibody in cats which had not been previously exposed."
U.S. Pat. No. 3,966,907 of Jarrett et al appears to be based on the research reported in the above-cited publication of Jarrett et al. It primarily discloses vaccines against feline leukemia which comprise cells infected with FeLV which have virus-associated antigen on their surfaces. However, in Example 7, a vaccine prepared from FeLV particles separated from cells is described. The viruses are treated for inactivation with 0.05% formalin, and are combined with Freund's incomplete adjuvant to prepare the vaccine dose, which contained approximately 10.sup.7 virus particles. On a protein weight basis, this is equivalent to about 0.001 to 0.002 milligrams of protein. There are also other reports in the literature of feline leukemia vaccines prepared from inactivated FeLV. See Yohn et al, Cancer Res., 36, 646-651 (1976); and Schaller et al, J. Natl. Cancer Inst., 59, 1441-1450 (1970). Yohn et al reported that no protection was provided by the vaccine, while Schaller et al found that the cats became more susceptible to tumor induction. With virus infected cell vaccines, Olsen et al reported that vaccinated cats are resistent to FeSV tumor induction but not to feline leukemia virus infection. Cancer Res., 35, 3642-3646 (1976).